One of the earliest histopathological signs of age-related hearing (loss (presbycusis) is the loss of the outer hair cells (OHC) in the cochlea. The vulnerability of the OHCs to the effects of age suggests that distortion product otacoustic emissions (DPOAE), which are believed to be associated with the OHC function, should serve as a useful tool for the assessment of the effects of age on the cochlea. The sensitivity of a DPOAE test of cochlear function depends on its stimulus parameters. At present it is not clear which combination of stimulus parameters are most suitable for the examination of the effects of age and age-related cochlear pathology on the cochlea. As a first step, in this application we propose to identify the DPOAE stimulus parameters which are optimally sensitive to the effects of age and age-related pathology. Optimally age-sensitive stimuli are defined as those that result in the largest change in DPOAE levels in the aged ears relative to young, normal DPOAE levels. To identify athe optimal stimuli, it is useful to consider that the DPOAEs are generated by normally functioning OHCs in a regions of overlap between the cochlear excitation patterns in response to two stimulus frequencies (f1 and f2, where f2 more f1). The amount of overlap between the excitation patters can be manipulated by the frequency separation between f1 and f2 or the level difference between L1 (level of f1 (level of f1) and L2 (level of f2) i.e., L1 - L2). As a starting point, we hypothesize that the frequency separation that results in the highest DPOAE levels in the normal cochlea, should also be the most sensitive to age-related changes. To evaluate this hypothesis, we propose to determine how DPOAE levels collected as a function of f2/f1 and L1 - L2 are altered in the aged cochleas. We will measure the 2f1 -f2 DPOAEs in the ears of aging mouse models of presbycusis, the CBA/J and C57BL/6J. The CBA mouse shows little loss of hearing sensitivity or cochlear pathology until late in life, whereas, the C57 mouse shows progressively severe elevation of hearing thresholds associated with a basoapical degeneration of cochlear hair cells beginning in young adulthood. The DPOAE data will be complemented by auditory brainstem evoked response threshold measures and cochlear hair cell counts using phalloidin-labelled actin expression. This study will identify candidate f2/f1 and L1 - L2 combinations which are optimally sensitive to age-related disruptions of the normal cochlea. Such candidate parameters could subsequently be evaluated in human subjects for sensitivity and specificity.